US3367930A - Process for the preparation of heterocyclic compounds - Google Patents
Process for the preparation of heterocyclic compounds Download PDFInfo
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- US3367930A US3367930A US399096A US39909664A US3367930A US 3367930 A US3367930 A US 3367930A US 399096 A US399096 A US 399096A US 39909664 A US39909664 A US 39909664A US 3367930 A US3367930 A US 3367930A
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- oxo
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- 238000000034 method Methods 0.000 title description 21
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 7
- 238000002360 preparation method Methods 0.000 title description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 24
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 18
- 230000008018 melting Effects 0.000 description 14
- 238000002844 melting Methods 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 11
- 238000007363 ring formation reaction Methods 0.000 description 11
- 229940003214 aluminium chloride Drugs 0.000 description 10
- -1 methylene, ethylene, substituted methylene Chemical group 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical class C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 5
- 239000005977 Ethylene Substances 0.000 description 5
- 239000012948 isocyanate Substances 0.000 description 5
- 150000002513 isocyanates Chemical class 0.000 description 5
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
- OXMPDOZBQGHTGH-UHFFFAOYSA-N 5h-benzo[b][1,4]benzoxazepin-6-one Chemical class O=C1NC2=CC=CC=C2OC2=CC=CC=C12 OXMPDOZBQGHTGH-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 125000001261 isocyanato group Chemical group *N=C=O 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 2
- 238000006675 Beckmann reaction Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 229940117389 dichlorobenzene Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 125000004043 oxo group Chemical group O=* 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- PELAWRHVRDOWQT-UHFFFAOYSA-N (2-amino-4-chlorophenyl)-phenylmethanone Chemical compound NC1=CC(Cl)=CC=C1C(=O)C1=CC=CC=C1 PELAWRHVRDOWQT-UHFFFAOYSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- IDWNSAXOQLJYOF-UHFFFAOYSA-N 11h-benzo[c][1]benzazepine Chemical class C1=NC2=CC=CC=C2CC2=CC=CC=C21 IDWNSAXOQLJYOF-UHFFFAOYSA-N 0.000 description 1
- CJKPKVLFYAXEBS-UHFFFAOYSA-N 2,3,6,7-tetrahydrooxazepine Chemical compound C1CC=CCNO1 CJKPKVLFYAXEBS-UHFFFAOYSA-N 0.000 description 1
- JZLUOCTZACJYNR-UHFFFAOYSA-N 2-(4-chlorophenyl)sulfanylaniline Chemical compound NC1=CC=CC=C1SC1=CC=C(Cl)C=C1 JZLUOCTZACJYNR-UHFFFAOYSA-N 0.000 description 1
- CBQAKBRASODKES-UHFFFAOYSA-N 2-(benzenesulfonyl)-3H-1,2-benzothiazole 1-oxide Chemical class C1(=CC=CC=C1)S(=O)(=O)N1S(C2=C(C1)C=CC=C2)=O CBQAKBRASODKES-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- UNOXQGBIAVFVBH-UHFFFAOYSA-N 2-benzyl-5-chloroaniline Chemical compound NC1=CC(Cl)=CC=C1CC1=CC=CC=C1 UNOXQGBIAVFVBH-UHFFFAOYSA-N 0.000 description 1
- RTERDTBXBYNZIS-UHFFFAOYSA-N 5h-benzo[b][1,4]benzothiazepin-6-one Chemical class O=C1NC2=CC=CC=C2SC2=CC=CC=C12 RTERDTBXBYNZIS-UHFFFAOYSA-N 0.000 description 1
- UHOLKGDSZJQEEB-UHFFFAOYSA-N 8-chloro-5h-benzo[b][1,4]benzothiazepin-6-one Chemical compound N1C(=O)C2=CC(Cl)=CC=C2SC2=CC=CC=C21 UHOLKGDSZJQEEB-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- XGIAHMUOCFHQTI-UHFFFAOYSA-N Cl.Cl.Cl.Cl.CC Chemical compound Cl.Cl.Cl.Cl.CC XGIAHMUOCFHQTI-UHFFFAOYSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 238000006085 Schmidt reaction Methods 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- 150000004056 anthraquinones Chemical class 0.000 description 1
- VMPVEPPRYRXYNP-UHFFFAOYSA-I antimony(5+);pentachloride Chemical compound Cl[Sb](Cl)(Cl)(Cl)Cl VMPVEPPRYRXYNP-UHFFFAOYSA-I 0.000 description 1
- XXRGLCKZBCIEKO-DLMDZQPMSA-N azocine Chemical compound C/1=C/C=C\N=C/C=C\1 XXRGLCKZBCIEKO-DLMDZQPMSA-N 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- ROJMAHHOFDIQTI-UHFFFAOYSA-L calcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate;hydron;piperazine Chemical compound [Ca+2].C1CNCCN1.OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ROJMAHHOFDIQTI-UHFFFAOYSA-L 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- TWXOQHRHGLZKFY-UHFFFAOYSA-N chembl1208809 Chemical compound C1=CC=C2C(=NO)C3=CC=CC=C3C(=O)C2=C1 TWXOQHRHGLZKFY-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- JGDFBJMWFLXCLJ-UHFFFAOYSA-N copper chromite Chemical compound [Cu]=O.[Cu]=O.O=[Cr]O[Cr]=O JGDFBJMWFLXCLJ-UHFFFAOYSA-N 0.000 description 1
- NPUACKRELIJTFM-UHFFFAOYSA-N cr gas Chemical class C1=NC2=CC=CC=C2OC2=CC=CC=C21 NPUACKRELIJTFM-UHFFFAOYSA-N 0.000 description 1
- XHRNQDMNINGCES-UHFFFAOYSA-N cyclohept-4-en-1-one Chemical compound O=C1CCC=CCC1 XHRNQDMNINGCES-UHFFFAOYSA-N 0.000 description 1
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate group Chemical group [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 150000003902 salicylic acid esters Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 150000004912 thiazepines Chemical class 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D281/16—[b, f]-condensed
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D267/02—Seven-membered rings
- C07D267/08—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D267/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D267/16—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D267/20—[b, f]-condensed
Definitions
- X denotes a member of the group consisting of oxygen, sulfur, methylene, ethylene, substituted methylene, and substituted ethylene
- B derivatives of (A) which contain in one or both benzene nuclei one or several substituents; which comprises subjecting isocyanates f the general formula:
- NCO E wherein X has the above-mentioned meaning, or derivatives thereof which contain substituents in one or both benzene nuclei, to cyclization by treatment with a condensing agent, such as aluminum chloride.
- heterocyclic compounds produced by the forego' ing process can be used as intermediates for preparing pharmaceuticals in accordance with the prior art teachmgs.
- the object of this invention is a process for preparing heterocyclic compounds of the formula:
- X denotes oxygen, sulfur, methylene, ethylene, substituted methylene, or substituted ethylene, such as monoalkylated or dialkylated methylene or ethylene, and which may contain in one or both benzene nuclei one or several substituents such as halogen, hydroxyl, nitro, trifluoromethyl, alkyl, alkoxy, alkylthio or similar residues.
- substituents such as halogen, hydroxyl, nitro, trifluoromethyl, alkyl, alkoxy, alkylthio or similar residues.
- X has the above-mentioned meaning and one or both benzene nuclei can contain substituents such as halogen, hydroxyl, nitro, trifiuoromethyl, alkyl, alkoxy, alkylthio or similar residues, are subjected to cyclization by treatment with a condensing agent, especially with aluminium chloride or polyphosphoric acid.
- a condensing agent especially with aluminium chloride or polyphosphoric acid.
- the cyclization is performed preferably at temperatures between about 80 and about 160 C. in a solvent having a correspondingly high boiling point, e.g. o-dichlorobenzene, using anhydrous aluminium chloride as the condensing agent.
- the usual catalysts for Friedel-Crafts-condensations such as tin tetrachloride, antimony pentachloride, boron trifiuoride, zinc dichloride, ferrichloride, hydrofluoric acid, phosphorus pentoxide, and similar compounds.
- the cyclization according to the present process can possibly lead to two different isomers, which are generally easy to separate by the 'usual methods, e.g. by fractionated crystallization.
- the cyclization according to the present process can possibly lead to two different isomers, which are generally easy to separate by the 'usual methods, e.g. by fractionated crystallization.
- 2-isocyanato-3'-chloro-diphenyloxide 1 chloro-10,1l-dihydro-l1-oxo-dibenz[b,f][l,4] oxazepine as well as the corresponding 3-chloro-compounds are obtained in a ratio of about 1:4.
- These com pounds can be separated by fractionated crystallization from pyridine (see Example 3). It is evident that in these circumstances the yield obtained with this method, which is practically quantitative, is for the sum of the two isomers.
- the substituents contained in the starting material not being inert in the conditions of the process can have a negative influence on the yield, e.g. methoxy residues may become partially demethylated so that one obtains a mixture of the corresponding methoxy and hydroxy derivatives of the product of Formula I; the hydroxy derivative can easily be re-methylated in the usual manner.
- the .isocyanates needed as starting compounds are obtained in practically quantitative yield from the corresponding amines by treatment with phosgene, preferably by using toluene as a solvent. They are colourless oils which can be distilled without being decomposed.
- Example 1 98 g. of anhydrous aluminium chloride in 900 ml. of o-dichlorobenzene are heated to l00 C. while being stirred. Within 15 minutes a solution of 183.2 g. of 2-isocyanato-4'-chlorodiphenylsulfide in 600 ml. of o-dichlorobenzene is added drop by drop, causing the temperature to rise to 120 C. Then the mixture is heated within one hour to 150 C., cooled and poured on to ice. The obtained mixture is subjected to distillation with steam. The residue is isolated by filtration and boiled with 700 ml. of acetone. One obtains 181 g.
- the compound can be identified as 2-chloro-10,11-dihydro- 11-oxo-dibenzo[b,f] [1,4]thiazepine by means of its melting point, its mixed melting point and its infra-red spec.- trum (potassium bromide) in comparison to the product obtained by thermic cyclization of 2-amino-2-carbomethoxy-4'-chloro-diphenylsulfide.
- Example 2 166.9 g. of 2-isocyanato-diphenyloxide are subjected to cyclization with 111 g. of anhydrous aluminium chloride in 1000 ml. of o-dichlorobenzene and the reaction mixture is worked up, using the same procedure as in Example 1.
- By crystallization from glacial acetic acid 163.5 g. (98% of the theoretical yield) of 10,11-dihydro-ll-oxo-dibenz- [b,f] [1,4]oxazepine are obtained in the form of colourless crystals, melting point 215217 C.
- mixed melting point and infra-red spectrum potassium bromide
- the product is found to be identical with a compound obtained by thermic cyclization of Z-amino- 2-carbomethoxydiphenyloxide.
- Example 3 143.2 g. of 2-isocyanat0-3"chloro-diphenyloxide (boiling point 125-130 C./0.07 Hg) are subjected to cyclization by treatment with 81.5 g. of anhydrous aluminium chloride in 1000 ml. of o-dichlorobenzene in the manner described in Example 1. There are obtained g. of a mixture with a melting point of 215-250 C., which is dissolved in 2500 ml. of pyridine, treated with carbon and subjected to fractional crystallization. One obtains in this way 110.5 g.
- Example 4 13 g. of anhydrous aluminium chloride are heated in 65 m1. of o-dichlorobenzene to a temperature of 80 C. A solution of 20.2 g. of 2 isocyanato 4 chloro diphenylmethane in 45 ml. of o-dichlorobenzene is added drop by drop while stirring the reaction mixture, which reaches a temperature of 105 C. The reaction mixture isthen stirred for one hour at 120 C., cooled to room temperature and poured on to 150 ml. of 2-n hydrochloric acid. The mixture obtained is subjected to distillation with steam. The resulting colourless crystals are isolated by filtration, washed with water and dried in vacuo at 80 C.
- the 2 isocyanato 4 chloro diphenylmethane with a boiling point of ll8121 C./O.1 Hg used as a starting material in this example may be obtained in a high yield by reducing 2 benzoyl 5 chloroaniline with hydrazine hydrate in a basic medium and treating the obtained 2- benzyl 5 chloroaniline with a 20% phosgene solution in toluene.
- Example 5 9.0 g. of 0 aminodibenzyl are dissolved in 10 ml. of absolute toluene. This solution is added drop by drop to 365 ml. of a 20% solution of phosgene in toluene, while 6 reached. After crystallization from acetone/ether, 4.0 g. of 5,6,11,12 tetrahydro 6 oxo dibenz[b,f] azocine are obtained in the form of colourless crystals, which upon recrystallization from chloroform/ether show a melting point of 240-243 C.
- X has the above-mentioned meaning, or derivatives thereof which contain substituents in one or both benzene nuclei, to cyclization by treatment with a condensing agent.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1238163A CH436303A (de) | 1963-10-09 | 1963-10-09 | Verfahren zur Herstellung siebengliedriger Heterocyclen |
| CH735564A CH440286A (de) | 1964-06-05 | 1964-06-05 | Verfahren zur Herstellung achtgliedriger N-Heterocyclen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3367930A true US3367930A (en) | 1968-02-06 |
Family
ID=25701181
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US399096A Expired - Lifetime US3367930A (en) | 1963-10-09 | 1964-09-24 | Process for the preparation of heterocyclic compounds |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US3367930A (de) |
| AT (1) | AT250367B (de) |
| BE (1) | BE654197A (de) |
| DE (1) | DE1470434A1 (de) |
| DK (1) | DK116438B (de) |
| GB (1) | GB1060786A (de) |
| NL (1) | NL6411504A (de) |
| SE (2) | SE327706B (de) |
Cited By (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3423402A (en) * | 1965-06-23 | 1969-01-21 | Ciba Ltd | Novel bibenzo(b,f)(1,4)oxazepin 11-ones |
| US3544561A (en) * | 1966-01-28 | 1970-12-01 | Boehringer Sohn Ingelheim | 10-substituted dibenz(b,f)(1,4)oxazepin-11(10h)-ones |
| US3546214A (en) * | 1967-07-11 | 1970-12-08 | Boehringer Sohn Ingelheim | Amino-substituted dibenz(b,f)(1,4)oxazepin-11(10h)-ones |
| US3910890A (en) * | 1972-10-20 | 1975-10-07 | Sandoz Ag | Preparation of morphanthridin-6-(5H)-ones |
| EP0419861A3 (en) * | 1989-08-29 | 1992-06-10 | Boehringer Ingelheim Pharmaceuticals Inc. | Dibenz(b,f)(1,4)oxazepin (and thiazepin)-11(10h)-ones and -thiones and their use in the prevention or treatment of aids |
| US5607929A (en) * | 1991-05-02 | 1997-03-04 | Glaxo Wellcome Inc. | Antiviral dibenzothiazepinone derivatives |
| US20030135042A1 (en) * | 2001-06-26 | 2003-07-17 | Neuromolecular, Inc. | Atypical antipsychotic agents having low affinity for the D2 Receptor |
| US20030134331A1 (en) * | 2000-05-10 | 2003-07-17 | The Trustees Of Columbia University | Controlling pathways that regulate muscle contraction in the heart |
| US20030235312A1 (en) * | 2002-06-24 | 2003-12-25 | Pessoa Lucio F. C. | Method and apparatus for tone indication |
| US20040048780A1 (en) * | 2000-05-10 | 2004-03-11 | The Trustees Of Columbia University In The City Of New York | Method for treating and preventing cardiac arrhythmia |
| US20040229781A1 (en) * | 2000-05-10 | 2004-11-18 | Marks Andrew Robert | Compounds and methods for treating and preventing exercise-induced cardiac arrhythmias |
| WO2004047722A3 (en) * | 2002-11-28 | 2004-12-02 | Sk Corp | METHOD OF PREPARING 10H-DIBENZO[b,f][1,4]THIAZEPIN-11-ONE |
| US20050187386A1 (en) * | 2002-11-05 | 2005-08-25 | Andrew Robert Marks | Novel anti-arrythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) |
| US20050186640A1 (en) * | 2000-05-10 | 2005-08-25 | Marks Andrew R. | Novel anti-arrythmic and heart failure drugs that target the leak in the ryanodine receptor (RYR2) |
| US20050192310A1 (en) * | 2004-03-01 | 2005-09-01 | Gavai Ashvinikumar V. | Fused heterotricyclic compounds as inhibitors of 17beta-hydroxysteroid dehydrogenase 3 |
| US20050215540A1 (en) * | 2004-01-22 | 2005-09-29 | Marks Andrew R | Novel anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof |
| US20050250753A1 (en) * | 2004-03-01 | 2005-11-10 | Fink Brian E | Fused tricyclic compounds as inhibitors of 17beta-hydroxysteroid dehydrogenase 3 |
| US20060293266A1 (en) * | 2000-05-10 | 2006-12-28 | The Trustees Of Columbia | Phosphodiesterase 4D in the ryanodine receptor complex protects against heart failure |
| US20070049572A1 (en) * | 2005-08-25 | 2007-03-01 | The Trustees Of Columbia University In The City Of New York | Novel agents for preventing and treating disorders involving modulation of the RyR receptors |
| US20070173482A1 (en) * | 2005-08-25 | 2007-07-26 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US7312044B2 (en) | 2003-03-07 | 2007-12-25 | The Trustees Of Columbia University In The City Of New York | Type 1 ryanodine receptor-based methods |
| US20110172190A1 (en) * | 2004-01-22 | 2011-07-14 | Andrew Robert Marks | Agents for preventing and treating disorders involving modulation of the ryanodine receptors |
| US8022058B2 (en) | 2000-05-10 | 2011-09-20 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US10918647B2 (en) * | 2016-07-26 | 2021-02-16 | University Of Southern California | Selective bromodomain inhibition of fungal Bdf1 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3337536A (en) * | 1963-01-03 | 1967-08-22 | Wander Ag Dr A | 10-(basic substituted)-dibenz[b, f][1, 4] oxazepinones |
-
1964
- 1964-09-16 GB GB37847/64A patent/GB1060786A/en not_active Expired
- 1964-09-24 US US399096A patent/US3367930A/en not_active Expired - Lifetime
- 1964-09-29 DE DE19641470434 patent/DE1470434A1/de active Pending
- 1964-09-30 AT AT834264A patent/AT250367B/de active
- 1964-10-02 NL NL6411504A patent/NL6411504A/xx unknown
- 1964-10-06 DK DK491264AA patent/DK116438B/da unknown
- 1964-10-08 SE SE06716/68A patent/SE327706B/xx unknown
- 1964-10-08 SE SE12098/64A patent/SE313568B/xx unknown
- 1964-10-09 BE BE654197A patent/BE654197A/xx unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3337536A (en) * | 1963-01-03 | 1967-08-22 | Wander Ag Dr A | 10-(basic substituted)-dibenz[b, f][1, 4] oxazepinones |
Cited By (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3423402A (en) * | 1965-06-23 | 1969-01-21 | Ciba Ltd | Novel bibenzo(b,f)(1,4)oxazepin 11-ones |
| US3544561A (en) * | 1966-01-28 | 1970-12-01 | Boehringer Sohn Ingelheim | 10-substituted dibenz(b,f)(1,4)oxazepin-11(10h)-ones |
| US3546214A (en) * | 1967-07-11 | 1970-12-08 | Boehringer Sohn Ingelheim | Amino-substituted dibenz(b,f)(1,4)oxazepin-11(10h)-ones |
| US3910890A (en) * | 1972-10-20 | 1975-10-07 | Sandoz Ag | Preparation of morphanthridin-6-(5H)-ones |
| EP0419861A3 (en) * | 1989-08-29 | 1992-06-10 | Boehringer Ingelheim Pharmaceuticals Inc. | Dibenz(b,f)(1,4)oxazepin (and thiazepin)-11(10h)-ones and -thiones and their use in the prevention or treatment of aids |
| AU639255B2 (en) * | 1989-08-29 | 1993-07-22 | Boehringer Ingelheim Pharmaceuticals, Inc. | Dibenz(b,f)(1,4)oxazepin(and thiazepin)-11(10h)-ones and-thiones |
| US5607929A (en) * | 1991-05-02 | 1997-03-04 | Glaxo Wellcome Inc. | Antiviral dibenzothiazepinone derivatives |
| US20040048780A1 (en) * | 2000-05-10 | 2004-03-11 | The Trustees Of Columbia University In The City Of New York | Method for treating and preventing cardiac arrhythmia |
| US20040229781A1 (en) * | 2000-05-10 | 2004-11-18 | Marks Andrew Robert | Compounds and methods for treating and preventing exercise-induced cardiac arrhythmias |
| US20060293266A1 (en) * | 2000-05-10 | 2006-12-28 | The Trustees Of Columbia | Phosphodiesterase 4D in the ryanodine receptor complex protects against heart failure |
| US20030134331A1 (en) * | 2000-05-10 | 2003-07-17 | The Trustees Of Columbia University | Controlling pathways that regulate muscle contraction in the heart |
| US20050186640A1 (en) * | 2000-05-10 | 2005-08-25 | Marks Andrew R. | Novel anti-arrythmic and heart failure drugs that target the leak in the ryanodine receptor (RYR2) |
| US8022058B2 (en) | 2000-05-10 | 2011-09-20 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US7393652B2 (en) | 2000-05-10 | 2008-07-01 | The Trustees Of Columbia University In The City Of New York | Methods for identifying a chemical compound that directly enhances binding of FKBP12.6 to PKA-phosphorylated type 2 ryanodine receptor (RyR2) |
| US20050222121A1 (en) * | 2001-06-26 | 2005-10-06 | Shitij Kapur | Atypical antipsychotic agents having low affinity for the D2 receptor |
| US20030135042A1 (en) * | 2001-06-26 | 2003-07-17 | Neuromolecular, Inc. | Atypical antipsychotic agents having low affinity for the D2 Receptor |
| US6890919B2 (en) | 2001-06-26 | 2005-05-10 | Shitij Kapur | Atypical antipsychotic agents having low affinity for the D2 receptor |
| US20030235312A1 (en) * | 2002-06-24 | 2003-12-25 | Pessoa Lucio F. C. | Method and apparatus for tone indication |
| US20050187386A1 (en) * | 2002-11-05 | 2005-08-25 | Andrew Robert Marks | Novel anti-arrythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) |
| US7544678B2 (en) | 2002-11-05 | 2009-06-09 | The Trustees Of Columbia University In The City Of New York | Anti-arrythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) |
| WO2004047722A3 (en) * | 2002-11-28 | 2004-12-02 | Sk Corp | METHOD OF PREPARING 10H-DIBENZO[b,f][1,4]THIAZEPIN-11-ONE |
| KR100707050B1 (ko) * | 2002-11-28 | 2007-04-13 | 에스케이 주식회사 | 10Ｈ-디벤조[ｂ,ｆ][1,4]티아제핀-11-온의 제조방법 |
| US7312044B2 (en) | 2003-03-07 | 2007-12-25 | The Trustees Of Columbia University In The City Of New York | Type 1 ryanodine receptor-based methods |
| US20050215540A1 (en) * | 2004-01-22 | 2005-09-29 | Marks Andrew R | Novel anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof |
| US7718644B2 (en) | 2004-01-22 | 2010-05-18 | The Trustees Of Columbia University In The City Of New York | Anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof |
| US20110172190A1 (en) * | 2004-01-22 | 2011-07-14 | Andrew Robert Marks | Agents for preventing and treating disorders involving modulation of the ryanodine receptors |
| US8710045B2 (en) | 2004-01-22 | 2014-04-29 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the ryanodine receptors |
| US20050250753A1 (en) * | 2004-03-01 | 2005-11-10 | Fink Brian E | Fused tricyclic compounds as inhibitors of 17beta-hydroxysteroid dehydrogenase 3 |
| US7417040B2 (en) | 2004-03-01 | 2008-08-26 | Bristol-Myers Squibb Company | Fused tricyclic compounds as inhibitors of 17β-hydroxysteroid dehydrogenase 3 |
| US20050192310A1 (en) * | 2004-03-01 | 2005-09-01 | Gavai Ashvinikumar V. | Fused heterotricyclic compounds as inhibitors of 17beta-hydroxysteroid dehydrogenase 3 |
| US20070173482A1 (en) * | 2005-08-25 | 2007-07-26 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US20070049572A1 (en) * | 2005-08-25 | 2007-03-01 | The Trustees Of Columbia University In The City Of New York | Novel agents for preventing and treating disorders involving modulation of the RyR receptors |
| US7704990B2 (en) | 2005-08-25 | 2010-04-27 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US7879840B2 (en) | 2005-08-25 | 2011-02-01 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US10918647B2 (en) * | 2016-07-26 | 2021-02-16 | University Of Southern California | Selective bromodomain inhibition of fungal Bdf1 |
Also Published As
| Publication number | Publication date |
|---|---|
| BE654197A (de) | 1965-04-09 |
| AT250367B (de) | 1966-11-10 |
| SE313568B (de) | 1969-08-18 |
| DE1470434A1 (de) | 1969-06-12 |
| GB1060786A (en) | 1967-03-08 |
| SE327706B (de) | 1970-08-31 |
| DK116438B (da) | 1970-01-12 |
| NL6411504A (de) | 1965-04-12 |
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